The research activities of the NorLux Neuro-Oncology Laboratory focus on brain tumor biology. The projects are carried out through a strategic colloboration with the Centre Researche Public Santé in Luxembourg (www.norlux.lu).

A major breakthrough in our studies was the establishment of a xenograft animal model that closely reflects the characteristics of high grade glioma. The model is based on serial transplantation of Glioblastoma tumor spheroids from patient material into the brain of immunodeficient rodents. Early generation rats show a highly infiltrative tumor phenotype, with no signs of angiogenesis. After serial passaging, the tumors become fully angiogenic and less invasive in late generation rats (Sakariassen et al. PNAS, 2006). This model has recently been adapted to GFP-expressing immunodeficient mice (Niclou et al. FASEB, 2008) and lays the basis to address seminal questions related to brain tumor initiation and progression.

Currently the research activities focus on the following two projects:

1. Tumor Host Interactions and Cancer Initiating Cells:
   The recently established immunodeficient GFP-expressing xenograft mouse model allows to separate human tumor cells from fluorescent host cells. This model is used to investigate the interaction between tumor cells and the host microenvironment with an emphasis on the induction of angiogenesis. Moerover we apply the model to isolate invasive cells with stem cell characteristics and address their role in tumor initiation. A particular focus will be on epigenetic mechanisms thought to regulate the behaviour of stem-like cancer cells in brain tumors.
2. Novel Molecular Targets against Angiogenesis:
   Solid tumor growth depends on a continuous supply of nutrients supplied from new blood vessels generated within the tumor. Gliomas in particular are highly vascularized tumors, and targeting these newly formed vessels (angiotargeting) is a promising new treatment strategy for gliomas. By applying high throughput proteomics techniques to brain tumors, we aim at identifying potential biomarkers involved in tumor angiogenesis that may represent novel drug targets to block neovascularization in brain tumors. This project is part of the Integrated Angiotargeting Project of the EU 6th FP.